|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | | The Internet audiocast of the CIRM board has resumed with discussion of changes in the biotech loan program. | | | | | | | | | | | | | | | | | | | | | | | | Directors of the California stem cell agency reconvened in public after a lengthy closed-door session during which they were believed to be discussing the election of a person to replace Robert Klein as chairman of the $3 billion enterprise.
The Internet audiocast of the event was up briefly but has now vanished. | | | | | | | | | | | | | | | | | | | | | | | | CIRM President Alan Trounson was generally pleased today with the report and recommendations of a blue-ribbon panel that reviewed the $3 billion stem agency's effort.
He made a presentation to the board at its meeting today in Irvine that was a bit truncated in the Internet audiocast. However, you can find a summary of his remarks (Power Point style) here. The bulleted points are his response. | | | | | | | | | | | | | | | | | | | | | | | | | The California stem cell agency today posted a press release on the report and recommendations by a blue-ribbon review panel that were discussed today at an Irvine meeting of its board of directors. The release contains quotes from both reviewers and board members. You can find it here. | | | | | | | | | | | | | | | | | | | | | | | | Directors of the $3 billion California stem cell agency are still meeting in closed session following a statement by its Chairman Robert Klein defending his actions in connection with an attempt to hand pick his successor.
The board went to lunch and into an executive session about two hours ago shortly after Klein orally laid out his view of what transpired in connection with the nomination of | | | | | | | | | | | | | | | | | | | | | | | | | Synergistic effect of adipose-derived stem cell therapy and bone marrow progenitor recruitment in ischemic heart. Lab Invest. 2010 Dec 6; Authors: Ii M, Horii M, Yokoyama A, Shoji T, Mifune Y, Kawamoto A, Asahi M, Asahara T Human multipotent adipose-derived stem cells (hMADSCs) have recently been isolated featuring extensive expansion capacity ex vivo. We tested the hypothesis that hMADSC transplantation might contribute to cardiac functional recovery by its direct or indirect effect on myocardial infarction (MI). Nude rats were either transplanted with hMADSCs or PBS (control) in ischemic myocardium immediately following MI. Echocardiographical assessment of cardiac function after MI with hMADSCs showed significant improvement of each parameter compared to that with PBS. Histological analysis also showed significantly reduced infarct size and increased capillary density in peri-infarct myocardium by hMADSC treatment. However, remarkable transdifferentiation of hMADSCs into cardiac or vascular lineage cells was not observed. Despite the less transdifferentiation capacity, hMADSCs produced robust multiple pro-angiogenic growth factors and chemokines, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and stromal cell-derived factor-1α (SDF-1α). Specifically, hMADSC-derived SDF-1α had a crucial role for cooperative angiogenesis, with the paracrine effect of hMADSCs and Tie2-positive bone marrow (BM) progenitor recruitment in ischemic myocardium. hMADSCs exhibit a therapeutic effect on cardiac preservation following MI, with the production of VEGF, bFGF, and SDF-1α showing paracrine effects and endogenous BM stem/progenitor recruitment to ischemic myocardium rather than its direct contribution to tissue regeneration.Laboratory Investigation advance online publication, 6 December 2010; doi:10.1038/labinvest.2010.191. PMID: 21135814 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Pitfalls of Cell-Systematic Evolution of Ligands by Exponential Enrichment (SELEX): Existing Dead Cells During In Vitro Selection Anticipate the Enrichment of Specific Aptamers. Oligonucleotides. 2010 Dec 6; Authors: Avci-Adali M, Metzger M, Perle N, Ziemer G, Wendel HP Aptamers represent auspicious ligands for recognition of target molecules on the surface of a specific cell population, such as stem or cancer cells. These ligands are able to capture and enrich desired cells from a cell mixture, and can be used for identification of new biomarkers, development of cell-specific therapeutics, and stem cell therapy. In this study, we investigated the influence of dead cells on single-stranded DNA (ssDNA) binding and established a method to eliminate dead cells from a cell suspension. Flow cytometry analyses demonstrated that all dead cells were stained with fluorescein-labeled ssDNA molecules. The increasing of the proportion of dead cells led to an increased number of cells that were positive for ssDNA staining. Using dead cell removal microbeads, the proportion of dead cells was significantly reduced. The studies demonstrated that dead cells lead to unspecific uptake/binding of ssDNA molecules during cell-Systematic Evolution of Ligands by Exponential enrichment (SELEX) and can cause failure of the selection process. Thus, the elimination of dead cell population before incubation with ssDNA molecules will reduce the loss of target binding sequences and the contamination of the enriched aptamer pool with unspecific ssDNA molecules caused by unspecific binding to dead cells. PMID: 21133818 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | Robert Klein, chairman of the California stem cell agency, today commented orally and briefly on his efforts to hand pick his successor at the $3 billion enterprise.
His remarks were a shorter and slightly altered version of the material he posted this morning on the agenda for today's CIRM directors meeting in Irvine. Klein made one important addition to the posted material. He indicated that | | | | | | | | | | | | | | | | | | | | | | | | | CIRM Chairman Robert Klein today posted a statement on the CIRM Web site regarding his attempt to engineer selection of his successor at the $3 billion stem cell agency. Klein's remarks were filed on the agenda for today's meeting of the CIRM board. It was not immediately clear whether he read the statement to the full board because the audiocast of the meeting began late and was interrupted from | | | | | | | | | | | | | | | | | | | | | | | | Directors of the California stem cell agency have just finished hearing the formal presentation of the report from the blue-ribbon review panel that recommended a strong push towards developing therapies and engaging the biotech industry, which has complained about its treatment by CIRM.
The directors took a short break and are scheduled to reconvene shortly. Some members of the public are | | | | | | | | | | | | | | | | | | | | | | | | | We will be bringing you live coverage of today's meeting of the governing board of the California stem cell agency at UC Irvine. We are monitoring the session via the Internet from El Salvador with a cellular connection from a sailboat in the Estero de Jaltepeque. Stories will be filed as warranted. The meeting is scheduled to get underway at 9:30 a.m. PST, but usually begins shortly after the | | | | | | | | | | | | | | | | | | | | | | | | The requirement that the chairman of the California stem cell agency be a citizen of California is unconstitutional according to a 1978 opinion by the state attorney general.
That's what James Harrison, outside counsel for CIRM, told the California Stem Cell Report early today. He was responding to an email query yesterday concerning the reason that Alan Bernstein, a Canadian, was scrubbed as | | | | | | | | | | | | | | | | | | | | | | | | | Synergistic effect of adipose-derived stem cell therapy and bone marrow progenitor recruitment in ischemic heart. Lab Invest. 2010 Dec 6; Authors: Ii M, Horii M, Yokoyama A, Shoji T, Mifune Y, Kawamoto A, Asahi M, Asahara T Human multipotent adipose-derived stem cells (hMADSCs) have recently been isolated featuring extensive expansion capacity ex vivo. We tested the hypothesis that hMADSC transplantation might contribute to cardiac functional recovery by its direct or indirect effect on myocardial infarction (MI). Nude rats were either transplanted with hMADSCs or PBS (control) in ischemic myocardium immediately following MI. Echocardiographical assessment of cardiac function after MI with hMADSCs showed significant improvement of each parameter compared to that with PBS. Histological analysis also showed significantly reduced infarct size and increased capillary density in peri-infarct myocardium by hMADSC treatment. However, remarkable transdifferentiation of hMADSCs into cardiac or vascular lineage cells was not observed. Despite the less transdifferentiation capacity, hMADSCs produced robust multiple pro-angiogenic growth factors and chemokines, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and stromal cell-derived factor-1α (SDF-1α). Specifically, hMADSC-derived SDF-1α had a crucial role for cooperative angiogenesis, with the paracrine effect of hMADSCs and Tie2-positive bone marrow (BM) progenitor recruitment in ischemic myocardium. hMADSCs exhibit a therapeutic effect on cardiac preservation following MI, with the production of VEGF, bFGF, and SDF-1α showing paracrine effects and endogenous BM stem/progenitor recruitment to ischemic myocardium rather than its direct contribution to tissue regeneration.Laboratory Investigation advance online publication, 6 December 2010; doi:10.1038/labinvest.2010.191. PMID: 21135814 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Stem and progenitor cells for neurological repair: Minor issues, major hurdles, and exciting opportunities for paracrine-based therapeutics. J Cell Biochem. 2010 Dec 6; Authors: Shimada IS, Spees JL The transplantation of cultured stem and progenitor cells is a key element in the rapidly growing field of regenerative medicine. Based on their ability to rescue and/or repair injured tissue and partially restore organ function, multiple types of stem/progenitor cells have already entered into clinical trials. However, despite several decades of intense research, the goal to apply culture-expanded stem/progenitor cells in a manner that can effectively replace cells after injury has yet to be realized. Many sources of potentially useful cells are available, but something is clearly missing. In addition, recent studies suggest that paracrine effects of secreted or released factors are responsible for most of the benefits observed after cell transplantation, rather than direct cell replacement. These data call into question the need for cell transplantation for many types of therapy, in particular for acute injuries such as myocardial infarction and stroke. In this review, we examine current progress in the area of cell transplantation and minor issues and major hurdles regarding the clinical application of different cell types. We discuss the "paracrine hypothesis" for the action of transplanted stem/progenitor cells as an opportunity to identify defined combinations of biomolecules to rescue and/or repair tissues after injury. Although many of the concepts in this review will apply to multiple injury/repair systems, we will focus primarily on stem/progenitor cell-based treatments for neurological disorders and stroke. © 2010 Wiley-Liss, Inc. PMID: 21136426 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | BMPs functionally replace Klf4 and support efficient reprogramming of mouse fibroblasts by Oct4 alone. Cell Res. 2010 Dec 7; Authors: Chen J, Liu J, Yang J, Chen Y, Chen J, Ni S, Song H, Zeng L, Ding K, Pei D Generation of induced pluripotent stem cells by defined factors has become a useful model to investigate the mechanism of reprogramming and cell fate determination. However, the precise mechanism of factor-based reprogramming remains unclear. Here, we show that Klf4 mainly acts at the initial phase of reprogramming to initiate mesenchymal-to-epithelial transition and can be functionally replaced by bone morphogenetic proteins (BMPs). BMPs boosted the efficiency of Oct4/Sox2-mediated reprogramming of mouse embryonic fibroblasts (MEFs) to ∼1%. BMPs also promoted single-factor Oct4-based reprogramming of MEFs and tail tibial fibroblasts. Our studies clarify the contribution of Klf4 in reprogramming and establish Oct4 as a singular setter of pluripotency in differentiated cells.Cell Research advance online publication 7 December 2010; doi:10.1038/cr.2010.172. PMID: 21135873 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Endothelial progenitor cells correlate with lesion volume and growth in acute stroke. Neurology. 2010 Dec 7;75(23):2059-2062 Authors: Bogoslovsky T, Chaudhry A, Latour L, Maric D, Luby M, Spatz M, Frank J, Warach S OBJECTIVES: Circulating endothelial progenitor cells (EPC) are markers of vascular injury and their numbers decrease in acute stroke. However, the relation of EPC levels to stroke severity has not been quantified. MRI measurements of lesion volume provide an objective method for stroke severity assessment and outcome prediction. This cross-sectional study aims to determine whether EPC are correlated with lesion volume at baseline, lesion growth, and final lesion volume. METHODS: Seventeen patients (median age 63 years, NIH Stroke Scale score 7) were selected from 175 patients with imaging-confirmed acute ischemic stroke. EPC were quantified by flow cytometry using CD34, CD133, and VEGFR2 surface markers. Brain MRI was performed at baseline and at days 1 and 5 after the stroke onset. Stroke lesion volumes were quantified. RESULTS: Larger lesion volumes measured on diffusion-weighted images (DWI) at baseline were associated with low EPC levels, while smaller lesion volumes and less lesion growth were linked with high levels of EPC subsets (CD34+CD133+, CD133+VEGFR2+, and CD34+ CD133+VEGFR2+). Similar results were observed with DWI lesion volumes and EPC (CD34+CD133+) on day 1. Lesion growth volume, represented as a difference between final lesion volume and baseline DWI, was larger in patients with lower day 1 EPC (CD133+VEGFR2+). After adjustments for age and admission glucose (model 1), mean arterial pressure and white blood cells (model 2), INR and hematocrit (model 3), the CD34+CD133+ subset remained predictive of baseline and day 1 lesion volumes, while CD133+VEGFR2+ predicted baseline lesion volume and growth of lesion volume. CONCLUSIONS: Higher EPC levels were indicative of smaller volumes of acute lesion, final lesion, and lesion growth, and may serve as markers of acute phase stroke severity. However, a larger prospective study is needed to confirm our findings. PMID: 21135380 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | The planarian flatworm: an in vivo model for stem cell biology and nervous system regeneration. Dis Model Mech. 2010 Dec 6; Authors: Gentile L, Cebrià F, Bartscherer K Planarian flatworms are an exception among bilaterians in that they possess a large pool of adult stem cells that enables them to promptly regenerate any part of their body, including the brain. Although known for two centuries for their remarkable regenerative capabilities, planarians have only recently emerged as an attractive model for studying regeneration and stem cell biology. This revival is due in part to the availability of a sequenced genome and the development of new technologies, such as RNA interference and next-generation sequencing, which facilitate studies of planarian regeneration at the molecular level. Here, we highlight why planarians are an exciting tool in the study of regeneration and its underlying stem cell biology in vivo, and discuss the potential promises and current limitations of this model organism for stem cell research and regenerative medicine. PMID: 21135057 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Probing cell migration in confined environments by plasma lithography. Biomaterials. 2010 Dec 4; Authors: Junkin M, Wong PK Cellular processes are regulated by various mechanical and physical factors in their local microenvironment such as geometric confinements, cell-substrate interactions, and cell-cell contact. Systematic elucidation of these regulatory mechanisms is crucial for fundamental understanding of cell biology and for rational design of biomedical devices and regenerative medicine. Here, we report a generally applicable plasma lithography technique, which performs selective surface functionalization on large substrate areas, for achieving long-term, stable confinements with length scales from 100 nm to 1 cm toward the investigation of cell-microenvironment interactions. In particular, we applied plasma lithography for cellular confinement of neuroblastomas, myoblasts, endothelial cells, and mammary gland epithelial cells, and examined the motion of mouse embryonic fibroblasts in directionality-confined environments for studying the effect of confinements on migratory behavior. In conjunction with live cell imaging, the distance traveled, velocity, and angular motion of individual cells and collective cell migration behaviors were measured in confined environments with dimensions comparable to a cell. A critical length scale that a cell could conceivably occupy and migrate to was also identified by investigating the behaviors of cells using confined environments with subcellular length scales. PMID: 21134692 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Immunopanning selection of A2B5-positive cells increased the differentiation efficiency of induced pluripotent stem cells into oligodendrocytes. Neurosci Lett. 2010 Dec 3; Authors: Ogawa SI, Tokumoto Y, Miyake J, Nagamune T Oligodendrocytes are the myelinating cells of the central nervous system (CNS), and defects in these cells can result in CNS dysfunction. Although oligodendrocyte precursor cell (OPC) transplantation therapy is an effective cure for several disorders, there is no readily available source of these cells. Recent studies have described the generation of induced pluripotent stem cell (iPSC) from somatic cells, leading to speculation that this technique might become a novel therapeutic tool in regenerative medicine. In a previous study, we were able to produce O4 positive (O4(+)) oligodendrocytes from mouse iPSC in vitro. Unfortunately, the efficiency of differentiation achieved was relatively low (2.3%). In the current study, we improved the differentiation efficiency using a mouse monoclonal antibody (A2B5) to select cells of oligodendrocyte lineage. During in vitro differentiation, we purified A2B5-positive (A2B5(+)) cells by immunopanning from a mixed culture of iPSC-derived cells. This procedure increased the differentiation efficiency of O4(+) oligodendrocytes to 43.5%. We also examined the expression of myelin basic protein (MBP), a marker of mature oligodendrocytes. After 21 days of terminal differentiation, 62.3% of iPSC-derived O4(+) oligodendrocytes expressed MBP. PMID: 21134419 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | STEM CELL DIFFERENTIATION INTO STEROIDOGENIC CELL LINEAGES BY NR5A FAMILY. Mol Cell Endocrinol. 2010 Dec 3; Authors: Miyamoto K, Yazawa T, Mizutani T, Imamichi Y, Kawabe SY, Kanno M, Matsumura T, Ju Y, Umezawa A Transformants of mesenchymal stem cells (MSCs) stably expressing Steroidogenic factor-1 (SF-1) undergo differentiation into steroidogenic cell-lineages by stimulation with cyclic-adenosine mono-phosphate (cAMP). Another member of NR5A nuclear orphan receptors, Liver-specific receptor homologue-1 (LRH-1), was also able to differentiate MSCs. On the other hand, we found that embryonic stem (ES) cells were hardly induced to differentiate into steroidogenic cell-lineage by the similar treatment. In this study, we developed a novel method to differentiate ES cells into steroidogenic cells. We introduced SF-1 into mouse ES cells at ROSA26 locus under regulation of Tetracycline-off (Tet-off) in order to express SF-1 in the cells at desired period. When SF-1 was induced to express after the ES cells had been differentiated into mesenchymal cell-lineage, steroid hormones were produced from the SF-1 expressing cells. This provides a safer method for supplying sufficient amount of differentiated cells towards future regenerative medicine. PMID: 21134412 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Retinoid X receptor gamma signaling accelerates CNS remyelination. Nat Neurosci. 2010 Dec 5; Authors: Huang JK, Jarjour AA, Oumesmar BN, Kerninon C, Williams A, Krezel W, Kagechika H, Bauer J, Zhao C, Evercooren AB, Chambon P, Ffrench-Constant C, Franklin RJ The molecular basis of CNS myelin regeneration (remyelination) is poorly understood. We generated a comprehensive transcriptional profile of the separate stages of spontaneous remyelination that follow focal demyelination in the rat CNS and found that transcripts that encode the retinoid acid receptor RXR-γ were differentially expressed during remyelination. Cells of the oligodendrocyte lineage expressed RXR-γ in rat tissues that were undergoing remyelination and in active and remyelinated multiple sclerosis lesions. Knockdown of RXR-γ by RNA interference or RXR-specific antagonists severely inhibited oligodendrocyte differentiation in culture. In mice that lacked RXR-γ, adult oligodendrocyte precursor cells efficiently repopulated lesions after demyelination, but showed delayed differentiation into mature oligodendrocytes. Administration of the RXR agonist 9-cis-retinoic acid to demyelinated cerebellar slice cultures and to aged rats after demyelination caused an increase in remyelinated axons. Our results indicate that RXR-γ is a positive regulator of endogenous oligodendrocyte precursor cell differentiation and remyelination and might be a pharmacological target for regenerative therapy in the CNS. PMID: 21131950 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Clinical applications of mesenchymal stem cells in soft tissue augmentation. Aesthet Surg J. 2010 Nov 1;30(6):838-42 Authors: Hanson SE, Gutowski KA, Hematti P Based on a variety of preclinical studies showing that mesenchymal stem cells (MSC) play a significant role in tissue repair and homeostasis, MSC have rapidly moved into a phase of clinical trials investigating their efficacy as a cell-based therapeutic modality for a diverse group of applications. An emerging body of evidence shows that in addition to being a progenitor cell population with self-renewing and multipotent differentiation capabilities, MSC have unique immunomodulatory properties, making them even more attractive for regenerative medicine. Emerging discoveries in stem cell biology have revealed a multitude of mechanisms through which MSC could potentially augment the current techniques in aesthetic surgery. In this article, the authors review the clinical advances in cell-based therapies relevant to aesthetic surgery, including tissue augmentation, rejuvenation, and regeneration. PMID: 21131458 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Human germ cell differentiation from fetal- and adult-derived induced pluripotent stem cells. Hum Mol Genet. 2010 Dec 3; Authors: Panula S, Medrano JV, Kee K, Bergström R, Nguyen HN, Byers B, Wilson KD, Wu JC, Simon C, Hovatta O, Reijo Pera RA Historically, our understanding of molecular genetic aspects of human germ cell development has been limited, at least in part due to inaccessibility of early stages of human development to experimentation. However, the derivation of pluripotent stem cells may provide the necessary human genetic system to study germ cell development. In this study, we compared the potential of human induced pluripotent stem cells (iPSCs), derived from adult and fetal somatic cells, to form primordial and meiotic germ cells, relative to human embryonic stem cells (hESCs). We found that approximately 5% of human iPSCs differentiated to primordial germ cells (PGCs) following induction with bone morphogenetic proteins (BMPs). Furthermore, we observed that PGCs expressed GFP from a germ cell-specific reporter and were enriched for expression of endogenous germ cell specific proteins and mRNAs. In response to overexpression of intrinsic regulators, we also observed that iPSCs formed meiotic cells with extensive synaptonemal complexes (SC) and post-meiotic haploid cells with a similar pattern of ACROSIN staining as observed in human spermatids. These results indicate that human iPSCs derived from reprogramming of adult somatic cells can form germ line cells. This system may provide a useful model for molecular genetic studies of human germ line formation and pathology and a novel platform for clinical studies and potential therapeutical applications. PMID: 21131292 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Robust MeO(2)MA/vinyl-4,6-diamino-1,3,5-triazine copolymer hydrogels-mediated reverse gene transfection and thermo-induced cell detachment. Biomaterials. 2010 Dec 3; Authors: Tang L, Yang Y, Bai T, Liu W We have fabricated a robust temperature sensitive hydrogel by photoinitiated copolymerization of 2-(2-methoxyethoxy)ethyl methacrylate (MeO(2)MA), 2-vinyl-4,6-diamino-1,3,5-triazine (VDT) and crosslinker polyethylene glycol diacrylate (PEGDA). It was shown that self-hydrogen bondings of VDT moieties in the bulk considerably strengthened the mechanical properties of gels, which was dependent on the weight ratio of MeO(2)/VDT and the initial monomer concentration; the VDT motifs on the surface could efficiently bind DNA for reverse gene transfection. On this soft-wet platform, gene expression lasted 7 days and the re-treated gels could be reused for new cycle of transfection. The gene modified cells could be detached by thermo-triggered switchable surface hydrophilicity of PMEO(2)MA in hydrogel. MTT assay showed low cytotoxicity of hydrogels. The results suggested that this type of mechanically strong H-bonded and thermoresponsive hydrogels hold a great potential as an integrated functional soft-wet platform for the unharmful harvest of gene modified seed cells for tissue engineering or as implantable scaffold for gene therapy and regenerative medicine applications. PMID: 21131046 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Effect of flow perfusion conditions in the chondrogenic differentiation of bone marrow stromal cells cultured onto starch based biodegradable scaffolds. Acta Biomater. 2010 Dec 2; Authors: Gonçalves A, Costa P, Rodrigues MT, Dias IR, Reis RL, Gomes ME Cartilage tissue engineering (TE) typically involves the combination of a 3D biodegradable polymeric support material, with primary condrocytes or other cell type able to differentiate into chondrocytes. Another important factor is the culture environment, which cell-material constructs are submitted to/accommodated. Different bioreactors have been introduced in TE approaches to provide specific culturing environments that might promote and accelerate cells potential for chondrogenic differentiation and enhance the production of cartilage extracellular matrix. The aim of the present study was to study the chondrogenic differentiation of goat bone marrow cells (GBMCs) under flow perfusion culture conditions. For that purpose, GBMCs were seeded into starch-polycaprolactone (SPCL) fiber mesh scaffolds and cultured in a flow perfusion bioreactor for up to 28 days using culture medium supplemented with TGF-β1. The tissue engineered constructs were characterized after several end points (7, 14, 21 and 28 days) by histological staining and immunocytochemistry analysis, as well as by GAGs and ALP quantification assays. Also, the expression of typical chondrogenic markers was assessed by real time RT-PCR analysis. In general, the results obtained suggest that flow perfusion microenvironment favors the chondrogenic potential of GBMCs. PMID: 21130906 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Contribution of IPS-1 to polyI:C-induced cytokine production in conjunctival epithelial cells. Biochem Biophys Res Commun. 2010 Dec 2; Authors: Ueta M, Kawai T, Yokoi N, Akira S, Kinoshita S We previously demonstrated that ocular surface epithelium expressed TLR3 and that its ligand, polyI:C, stimulation induced the secretion of inflammatory cytokines and type I IFN. It was recently reported that RIG-I and MDA5 also recognize viral dsRNA mimicking polyI:C. In this study, we investigated whether RIG-I and/or MDA5 contribute to polyI:C-inducible responses in conjunctival epithelium. The expression of RIG-I, MDA5, and TLR3 in human conjunctival epithelium was examined by RT-PCR and their up-regulation after polyI:C stimulation by quantitative RT-PCR and immunoblot analysis. Human conjunctival epithelial cells also expressed RIG-I, MDA-5 and TLR3 mRNA and protein. The expression of RIG-I and MDA-5, but not of TLR3, was markedly up-regulated upon polyI:C stimulation. We also examined the function of IPS-1 (an adaptor molecule common to RIG-I and/or MDA5) and TLR3 in conjunctival epithelium using IPS-1 KO and TLR3 KO mice To analyze in vivo murine conjunctival epithelial cells, 10 μl of a 100 μg/ml polyI:C solution were delivered subconjunctivally and as eye drops, then conjunctival epithelial cells were subjected to gene expression analysis. We focused on 10 transcripts up-regulated in murine conjunctival epithelium upon polyI:C stimulation. Cxcl10, Mx1, Ifi44, Ifi203, Iigp2 and Rtp4 were dominantly regulated by IPS-1, Ccl5 by TLR3, and Rsad2,Mx2 and Cmpk2 were regulated by TLR3 and IPS-1. Our results showed that conjunctival epithelial cells express RIG-I and MDA5, and IPS-1, an adaptor molecule common to RIG-I and MDA5, contributes to polyI:C-inducible cytokine production in conjunctival epithelial cells. PMID: 21130742 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Reconstitution of coronary vasculature in ischemic hearts by plant-derived angiogenic compounds. Int J Cardiol. 2010 Dec 2; Authors: Chen H, Peng P, Cheng L, Lin X, Chung SS, Li M BACKGROUND: Coronary heart diseases (CHD) remain the most prevalent cause of premature death. Substantial growth of new collateral coronary vessels to the ischemic region would provide reconstitution of the occluded arteries and correction of heart ischemia. However, this remains an impossible mission with current advances. METHODS: Incomplete ligation of left anterior descending (LAD) coronary artery was applied in rat resulting in partial occlusion of LAD. This chronic CHD model was employed to assess the therapeutic angiogenesis of Angio-T using ECG and echocardiography. Histological analysis was performed to provide substantial evidence for therapeutic angiogenesis in ischemic hearts with the possible involvement of JAK-STAT signaling pathway investigated. RESULTS: Angio-T stimulated growth of new collateral microvessels in ischemic hearts and progressively improved heart functional performance 2weeks post treatment. The involvement of JAK/STAT signaling pathway in Angio-T stimulated growth of new collateral coronary vessels in ischemic hearts was demonstrated. CONCLUSIONS: The substantial therapeutic angiogenesis of Angio-T in ischemic hearts was demonstrated that may provide a more effective solution for non-interventional treatment of chronic CHD. PMID: 21130507 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Fabrication and characterization of tunable polysaccharide hydrogel blends for neural repair. Acta Biomater. 2010 Dec 1; Authors: Zuidema JM, Pap MM, Jaroch DB, Morrison FA, Gilbert RJ Hydrogels are an important class of biomaterials that have the potential to be used as three-dimensional tissue engineering scaffolds for regenerative medicine. This is especially true in the central nervous system, where neurons do not have the ability to regenerate due to the prohibitory local environment following injury. Hydrogels can fill an injury site, replacing the growth-prohibiting environment with a more growth permissive one. In this study, dextran and chitosan were incorporated into a methylcellulose and agarose hydrogel blend. This created several thermally sensitive polysaccharide hydrogel blends that had tunable mechanical and surface charge properties. Cortical neurons were cultured on the hydrogels to determine the blend that had the greatest neuron compatibility. Our results show that softer, more positively charged polysaccharide hydrogel blends allow for greater neuron attachment and neurite extension, showing their promise as CNS regeneration scaffolds. PMID: 21130187 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Differentiation and regeneration potential of mesenchymal progenitor cells derived from traumatized muscle tissue. J Cell Mol Med. 2010 Dec 3; Authors: Jackson WM, Lozito T, Djouad F, Kuhn NZ, Nesti LJ, Tuan RS Mesenchymal stem cell (MSC) therapy is a promising approach to promote tissue regeneration by either differentiating the MSCs into the desired cell type or by using their trophic functions to promote endogenous tissue repair. These strategies of regenerative medicine are limited by the availability of MSCs at the point of clinical care. Our laboratory has recently identified multipotent mesenchymal progenitor cells (MPCs) in traumatically injured muscle tissue, and the objective of this study was to compare these cells to a typical population of bone marrow-derived MSCs. Our hypothesis was that the MPCs exhibit multilineage differentiation and expression of trophic properties that make functionally them equivalent to bone marrow-derived MSCs for tissue regeneration therapies. Quantitative evaluation of their proliferation, metabolic activity, expression of characteristic cell-surface markers and baseline gene expression profile demonstrate substantial similarity between the two cell types. The MPCs were capable of differentiation into osteoblasts, adipocytes and chondrocytes, but they appeared to demonstrate limited lineage commitment compared to the bone-marrow derived MSCs. The MPCs also exhibited trophic (i.e., immunoregulatory and pro-angiogenic) properties that were comparable to those of MSCs. These results suggest that the traumatized muscle-derived MPCs may not be a direct substitute for bone marrow-derived MSCs. However, because of their availability and abundance, particularly following orthopaedic injuries when traumatized muscle is available to harvest autologous cells, MPCs are a promising cell source for regenerative medicine therapies designed to take advantage of their trophic properties. PMID: 21129154 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Bone regeneration and stem cells. J Cell Mol Med. 2010 Dec 3; Authors: Arvidson K, Abdallah BM, Applegate LA, Baldini N, Cenni E, Gomez-Barrena E, Granchi D, Kassem M, Konttinen YT, Mustafa K, Pioletti DP, Sillat T, Finne-Wistrand A This invited review covers research areas of central importance for orthopedic and maxillofacial bone tissue repair, including normal fracture healing and healing problems, biomaterial scaffolds for tissue engineering, mesenchymal and fetal stem cells, effects of sex steroids on mesenchymal stem cells, use of platelet rich plasma for tissue repair, osteogenesis and its molecular markers. A variety of cells in addition to stem cells, as well as advances in materials science to meet specific requirements for bone and soft tissue regeneration by addition of bioactive molecules, are discussed. PMID: 21129153 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | In vitro models of pancreatic differentiation using ES or iPS cells. Congenit Anom (Kyoto). 2010 Dec 5; Authors: Higuchi Y, Shiraki N, Kume S Embryonic stem cells or induced pluripotent stem cells are expected as a surrogate cell source for regenerative medicine. Today, many researchers have reported the differentiation method of insulin-expressing pancreatic β cells from ES or iPS cells. However, the detailed molecular mechanisms underlying the differentiation of ES or iPS cells into the pancreatic lineages are still unclear. We have established a feeder cell based differentiation system into the pancreatic progenitor cells, and revealed the signaling pathways that are involved in the differentiation of ES cells into the mesendoderm, endoderm and pancreatic progenitor cells. Recently, we have demonstrated that the extra-cellular environment, particularly the laminin-integrin signaling and heparan sulfate proteoglycan, is important for the regionalization of definitive endoderm cells into pancreatic lineages. These results provide new insights for the differentiation mechanism of pancreatic cell lineages. PMID: 21129040 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | The Implications of Human Stem Cell Differentiation to Endothelial Cell via Fluid Shear Stress in Cardiovascular Regenerative Medicine: A Review. Curr Pharm Des. 2010 Dec 3; Authors: Tan A, Sumpio BE, Lee S, Seifalian AM Stem cell therapy heralds a new chapter in cardiovascular regenerative medicine. Cardiovascular implants are often used in both surgery and interventional cardiology. Cardiovascular stents are utilized in percutaneous coronary interventions (PCI), and are classified as either bare metal stents (BMS) or drug-eluting stents (DES). Although DES might decrease the risk of vascular restenosis, there are complications (e.g. thrombosis) associated with it as well. Many new and novel composite materials are increasingly being developed along the premise of mobilizing and attracting endogenous stem cells to home-in and differentiate into a confluent layer of endothelial cell around the vessel wall. One of the main forces acting on cells in a blood vessel wall is fluid shear stress. Fluid shear stress is vital in establishing the vasculature of the embryo, and different shear stress patterns have been both implicated in maintaining vascular physiology, and also associated with certain pathological conditions. Recent evidence suggests that via a plethora of mechanosensors and mechanotransduction signaling pathways, stem cells differentiate into endothelial cells when exposed to fluid shear stress. Here we review the current knowledge pertaining to the roles that mechanosensors and mechanotransducers play in stem cell differentiation into endothelial cells via fluid shear stress, and its implications for pharmacological applications and cardiovascular implants in the realm of regenerative medicine. PMID: 21128890 [PubMed - as supplied by publisher] | | | | | | | | | |  | |  | |  |
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